The ability of older adults to perform routine daily activities is compromised by the loss of muscle mass (sarcopenia) and reduced power, and the problem is exacerbated by the development of muscle fatigue. This proposal will address these issues by studying fatigue induced by dynamic contractions in older men and women (= 70 years). We take a translational approach by examining the mechanisms of fatigue from dynamic contractions of single fibers (from muscle biopsies), whole muscle (magnetic resonance spectroscopy, MRS) and within the neuromuscular system (using transcranial magnetic stimulation, TMS). The hypothesis is that older adults fatigue more rapidly than young adults during dynamic contractions due to age-related inefficiencies inherent to skeletal muscle fiber (peripheral fatigue) rather than greater fatigue in the central nervous system (central fatigue). Our experimental design includes a comprehensive study of both men and women to examine sex differences. This is particularly important given the realization that fatigability in older women has received minimal attention despite the greater vulnerability to older women. A secondary goal is to test a novel exercise paradigm in protecting older adults from fatigue. The hypothesis is that training with slow six second shortening and six second lengthening contractions at velocities and forces known to elicit peak power will improve whole muscle and body performance, muscle fiber size and function in older adults to a greater extent than traditional high resistance (80% of one repletion maximum) contractions. In Aim 1, we will study single fibers obtained by needle biopsy from the vastus lateralis muscle to compare single fiber function, economy and fatigue in young and old sedentary men and women, and old late-life exercisers (exercisers for ~the last 10 years) and old life-long exercise groups. Our hypothesis is that fiber function in older adults is compromised mainly during dynamic contractions by a reduced peak power, rate of tension development, and economy, while isometric force is well maintained. Our preliminary data also suggests that muscle fibers from older adults are more sensitive to the fatiguing effects of low pH and high inorganic phosphate. We expect fast fibers to be more effected by age than slow fibers, and the functional loss to be non-exercisers>late-life exercisers>life-long exercisers. Aim 2 will test the hypothesis that age-induced change in peripheral fatigue of whole muscle is increased during dynamic exercise resulting in greater muscle fatigue compared with young adults. We will use TMS to assess fatigue in the whole muscle and to show that central fatigue does not differ with age for dyanmic fatiguing contractions. In Aim 3, we will test the effectiveness of the novel exercise training and the hypothesis that it will improve whole body tasks, whole muscle and single fiber performance (peak power and metabolism), and resistance to fatigue. Muscle biopsies, TMS and MRS will be performed before and after training. These outcomes will provide important new information that will translate into clinically important exercise programs to improve quality of life and reduce health care costs with aging.